This invention is directed to an implantable neurostimulator having improved efficacy in treating epilepsy and other neurological disorders, and particularly in reducing the incidence of epileptic seizures, and also to processes of using that neurostimulator.
Epileptic seizures are characterized by excessive or abnormally synchronous neuronal activity. Neurologists recognize a wide variety of seizures. Partial onset seizures begin in one part of the brain; general onset seizures arise throughout the entire brain simultaneously. When partial onset seizures progress to involve much of the brain, they are said to have xe2x80x9csecondarily generalized.xe2x80x9d Some seizures result in the loss of conscious awareness and are termed xe2x80x9ccomplexxe2x80x9d seizures. So-called xe2x80x9csimplexe2x80x9d seizures may involve other symptoms, but consciousness is unimpaired. Seizure symptoms may include sensory distortions, involuntary movements, or loss of muscle tone. The behavioral features of a seizure will often reflect a function of the cortex where the abnormal electrical activity is found.
Physicians have been able to treat epilepsy by resecting certain brain areas by surgery and by medication. Brain surgery is irreversible, and is ineffective or is associated with neural morbidity in a sizable percentage of cases. Medication is the most prevalent treatment for epilepsy. It is effective in over half of patients, but in the reminder of the patients, the medication is either ineffective in controlling seizures, or the patients suffer from debilitating side effects. A more promising method of treating patients having epileptic seizures is by electrical stimulation of the brain.
Since the early 1970""s, electrical brain stimulators have been used to provide more or less constant stimulation, the stimulation largely being unrelated to detected electrical activity.
Electrical stimulation of the nervous system has been used to suppress seizures. A device is described in Cooper et al. for stimulation of the cerebellum. See, xe2x80x9cThe Effect of Chronic Stimulation of Cerebellar Cortex on Epilepsy and Man,xe2x80x9d I. S. Cooper et al. in The Cerebellum, Epilepsy and Behavior, Cooper, Riklan and Snyder eds., Plenum Press, New York, 1974. Others have utilized devices that stimulate the centromedian nucleus of the thalamus. See, xe2x80x9cElectrical Stimulation of the Centromedian Thalamic Nucleus in Control of Seizures: Long Term Studies,xe2x80x9d F. Velasco et al, Epilepsia, 36 (1): 63-71, 1995. Chaos Theory has been used to apply stimulation to a seizure focus in vitro to abort the seizure. See S. Schiff et al, xe2x80x9cControlling Chaos in the Brain,xe2x80x9d Nature, 370: 615-620, Aug. 25, 1994.
Non responsive electrical stimulation devices have been used for significant periods. The devices and procedures did not constitute a panacea, however. For instance, a seventeen-year follow-up study shown in Davis et al. (xe2x80x9cCerebellar Stimulation for Seizure Control 17 Year Study,xe2x80x9d Proceedings of the Meeting of the American Society for Stereotactic and Functional Neurosurgery, Pittsburgh, Pa., Jun. 16-19, 1991 and in Stereotact. Funct. Neurosurg. 1992; 58: 200-208) showed that less than one-half of the patients became seizure free, even though 85% showed some benefit.
In contrast, responsive stimulation, specifically electrical stimulation that is applied to the brain, has not yet been used to treat patients in long-term studies. This is true even though there are algorithms suitable for detection of the onset of an epileptic seizure. For instance, Qu et al. provide an algorithm said to recognize patterns of electrical activity similar to those developed while recording an actual epileptic seizure. See, Qu et al., xe2x80x9cA Seizure Warning System for Long-Term Epilepsy Monitoring,xe2x80x9d Neurology 1995; 45: 2250-2254. Similarly, Osorio, et al. have suggested an algorithm applied to signals from intracranial electrodes with good results. See Osorio et al., xe2x80x9cA Method For Accurate Automated Real-Time Seizure Detection,xe2x80x9d Epilepsia 1995, 36(supp. 4).
None of the cited documents describes procedures in which a non-responsive electrical stimulation signal is applied to the brain in a first mode and, upon detection of impending or of extant epileptiform electrical activity, a second responsive mode of stimulation is applied to the brain either with or without cessation of non-responsive stimulation.
The neurostimulator disclosed herein itself generally involves two modes of electrical stimulation: the first involves delivering a non-responsive electrical stimulation signal which is applied to the central nervous system to reduce the likelihood of a seizure or other undesirable neurological even from occurring, and a second mode that involves delivering electrical stimulation signal or signals when epileptiform waveforms are impending or extant.
The responsive electrical stimulation signal or signals are intended to terminate epileptiform activity, e.g., to desynchronize abnormally synchronous brain electrical activity.
Alternatively, the second mode may be used to deliver sensory stimulation, e.g., a scalp or sound stimulation, to the patient rather than deliver electrical stimulation to the patient.
Finally, the neurostimulator may be used by a physician to induce epileptiform activity and then verify the effectiveness of the parameters of the neurostimulation signals.
The invention is an implantable neurostimulator having improved efficacy in treating epilepsy and other neurological disorders and processes of using that neurostimulator. The method generally includes three or more steps. Initially, a non-responsive electrical stimulation signal is applied to the brain in a non-responsive mode. Secondly, some brain electrical activity is detected either during the non-responsive stimulation signal or after the non-responsive stimulation signal is paused. Third, when that detected electrical activity shows impending or existing epileptiform brain electrical activity, a second electrical stimulation signal is applied to the brain. Alternatively, a sensory stimulation, e.g., sound or scalp twitch, may be directed to the patient in place of or in addition to the second electrical stimulation signal.
The first or non-responsive electrical stimulation signal may or may not be paused during the second phase as desired. The non-responsive stimulation may be diurnally varied or varied on some other schedule as desired. The brain electrical activity may be detected in a variety of ways including scalp electrodes, cortical electrodes, or the electrical activity may be monitored at a depth within the brain. The responsive electrical stimulation signal may be applied to one or more electrodes placed on or about the brain. If multiple electrodes are chosen, either for measurement of the brain electrical activity or application of the responsive stimulation, the electrodes may be chosen so that they are independently selectable if so desired. The responsive stimulation (and the non-responsive stimulation) may be defined by parameters such as the electrode or electrodes selected, pulse width, inter-pulse interval (or frequency), pulse amplitude, pulse morphology (including the use of continuous waveforms such as trapezoidal, quasi-sinusoidal or sinusoidal morphologies, or pulse morphologies where each phase of the pulse is triangular, trapezoidal, a haversine, or other shape), the number of pulses in the burst (or the number of cycles, if a continuous waveform morphology is used), the number of bursts, and the intervals between bursts. Each of these parameters for either the responsive or the non-responsive stimulation may be changed or left static during a mode of the process.
The procedure may include a pause of the responsive stimulation for detection of or measurement of brain electrical activity. This may then be followed by either re-commencement of the non-responsive stimulation, or, if the desired cessation of epileptiform activity has not been achieved, by a continuation of the responsive stimulation.
The procedure may also include the step of using the implanted neurostimulator to apply electrical stimulation to the brain under physician control to cause epileptiform activity and a second step of using the implanted neurostimulator to apply a responsive stimulation signal which terminates that epileptiform activity. This permits the neurostimulator to be used to test the effectiveness of the parameters selected for responsive stimulation. The testing may be done before, during, or anytime after implantation of the inventive neurostimulator to assess functionality. In addition, the testing may be used to verify the effectiveness of the non-responsive stimulation parameters by assessing the relative ease or difficulty in initiating epileptiform activity.
In general, the implantable neurostimulator includes at least a first brain electrical activity sensor near or in contact with the brain, at least a first stimulator electrode for providing a non-responsive stimulation to the brain and optionally for providing the responsive stimulation, a non-responsive signal source for the first stimulation electrode, one or more (optional) second stimulator electrodes for providing the responsive stimulation, and a responsive stimulation source. The non-responsive and responsive sources may be integrated into a single source if so desired.
Desirably there may be one, two or multiple brain electrodes. When one electrode is used, the electrode is placed in a location in the brain that is best suited to terminating the patient""s seizure with the responsive mode stimulation (typically near the epileptogenic region or a neural pathway involved in sustaining or propagating epileptiform activity which may be within a neural relay such as a thalamic structure). If there are two electrodes, the first is used for non-responsive stimulation and positioned in or on the cerebellum or in a deep brain structure such as the thalamus, basal ganglia and related structures, hippocampus or amygdala, the second used for responsive stimulation and placed on or near the seizure focus or a neural pathway involved in sustaining or propagating the epileptiform activity. In some variations of the invention, the patient will benefit from a larger number of electrodes being used. In addition to the responsive mode stimulation, scheduled stimulation is delivered to reduce the incidence of spontaneously arising seizures.
A neurostimulator according to the invention has an enhanced ability to terminate epileptiform activity, is less likely to generalize ongoing epileptiform activity, optimally controls seizures by lowering the incidence of seizures as well as treating instances of breakthrough epileptiform activity, and provides for optimization of stimulation parameters programmed into the implanted neurostimulator.